Spectacular advances in the ability to manipulate, fabricate and alter tiny subjects at the nanometer scale (Nanotechnology) revolutionized material science in the past decade. The recent application of nanotechnology to life sciences has shown exciting promises in a wide range of disciplines. The development of laser-based technology (confocal microscope, laser tweezers, laser scissors, mutilphoton excitation confocal microscope, near field microscope, etc.) now allows functional imaging of living cells in thick tissues; the manipulation of single molecules, single organelles and single cells; the determination of the binding force and rate of interaction of DNA and other single molecules; the surgery of chromosomes and organelles in a living cell and the fabrication of miniature medical devices. The development of scanning probe microscopy (atomic force, scanning tunneling and electrochemical probe, near field microscopy) has enabled the manipulation of single molecules, the preparation of novel biochips and biosensors, and the measurement of physical and spectroscopic properties of single molecules in living cells. In the past year since our arrival at NIH, our workgroup have succeeded in establishing state-of-the-art facilities (laser tweezer, atomic force microscope, cellular force microscope, single fiber force station, real time confocal microscope, single molecule fluorescence microscope, and digital image analysis) to apply, adapt and develop bio-nanotechnology. These techniques are being applied to study single motors such as myosin and kinesin as well elastic proteins such a titin and nebulin, muscle filaments, cytoskeletal filaments, receptors in cellular membranes and cellular organelles such as myofibril, ribosome and chromatin. More specifically, our goals are: a. Measuring the mechanical property and spectroscopy of single molecules, organelles and single cells. b. Measuring the strength, speed and movement of interacting single molecules/organelles/cells. c. Manipulating and altering intracellular organelles in living cells. d. Fabricating and designing new instrumentation in nanotechnology. These direct measurement and manipulation of single molecule and filaments and organelles will provide unique and important insights of the events in the assembly and function of contractile machinery in muscle and nonmuscle cells. These studies will also reveal important engineering principles for designing tissues with prescribed mechanical properties.